Abstract
BackgroundProstate cancer is a leading cause of death in the male population of the western world. Human kallikrein-related peptidase 2 (hK2) is abundantly expressed in malignant prostatic tissue, and its gene, KLK2, is regulated by the androgen receptor. 11B6 is a murine IgG1 monoclonal antibody directed against free human hK2. In this study, we performed a preclinical evaluation of 111In-labelled 11B6 in mouse xenografts to investigate its potential in the clinical staging and assessment of metastatic prostate cancer.Methods11B6 was radiolabelled with 111In through CHX-A″-DTPA chelation. In vivo biodistribution and uptake of 111In-DTPA-11B6 were measured until 168 h post-injection in NMRI nude mice bearing subcutaneous LNCaP xenografts. The binding specificity to hK2 was evaluated by both in vivo competitive binding assays with excess non-labelled 11B6 and hK2-negative DU145 xenografts. SPECT/CT imaging of subcutaneous and intra-tibial LNCaP xenografts was used to visualize the tumours.ResultsTumour uptake of 111In-DTPA-11B6 in LNCaP xenografts was 19% ± 0.78%IA/g at 48 h, giving a tumour-to-blood ratio of 1.6, which increases to 2.4 at 1 week post-injection. Accumulation was low in other organs except for the salivary glands, which is probably the result of cross-reactivity with mouse kallikreins. Significantly lower tumour accumulation was observed in competitive assays and DU145 xenografts. SPECT/CT imaging could clearly visualize the subcutaneous and intra-tibial LNCaP xenografts.ConclusionsOur study demonstrates the potential of 111In-DTPA-11B6 for the detection of metastatic prostate cancer and monitoring anti-androgen therapy, as it exhibits an increased uptake and accumulation in viable tumour when compared to normal tissue. A humanised version of the 11B6 monoclonal antibody is currently under evaluation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-014-0051-5) contains supplementary material, which is available to authorized users.
Highlights
Prostate cancer is a leading cause of death in the male population of the western world
Molecular imaging methods based on metabolic markers such as 18F-FDG and 18F/11C-Choline are commonly used; there are known limitations for these tracers. 18F-FDG works well in a more advanced disseminated disease, but is ineffective in detecting localized prostate cancer (PCa) because of its lower glycolytic uptake compared to other neoplasms [4]
The normal elimination of 18F-FDG through the urinary bladder can mask the uptake in the prostate and regional lymph nodes [5]. 18F/11C-Choline is the most common radiotracer in PCa imaging today, and while they perform better than 18F-FDG, they are still limited in their ability to differentiate between a localized PCa and benign disease [6]
Summary
Prostate cancer is a leading cause of death in the male population of the western world. We performed a preclinical evaluation of 111In-labelled 11B6 in mouse xenografts to investigate its potential in the clinical staging and assessment of metastatic prostate cancer. SPECT/CT imaging of subcutaneous and intra-tibial LNCaP xenografts was used to visualize the tumours. Results: Tumour uptake of 111In-DTPA-11B6 in LNCaP xenografts was 19% ± 0.78%IA/g at 48 h, giving a tumour-toblood ratio of 1.6, which increases to 2.4 at 1 week post-injection. Conclusions: Our study demonstrates the potential of 111In-DTPA-11B6 for the detection of metastatic prostate cancer and monitoring anti-androgen therapy, as it exhibits an increased uptake and accumulation in viable tumour when compared to normal tissue. 18F/11C-Choline is the most common radiotracer in PCa imaging today, and while they perform better than 18F-FDG, they are still limited in their ability to differentiate between a localized PCa and benign disease [6]. Preliminary clinical studies demonstrated that 18F-FDHT might provide for the imaging of AR expression during disease progression in castration-resistant PCa [8]
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